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TUMOR NECROSIS FACTOR-Α AND TUMOR NECROSIS FACTOR-Β SINGLE NUCLEOTIDE POLYMORPHISM AND CHRONICITY IN EGYPTIAN PEDIATRIC PATIENTS WITH IMMUNE THROMBOCYTOPENIA.
Author(s): ,
Nesrine El-Gharbawi
Affiliations:
Clinical and Chemical Pathology,Faculty of Medicine, Cairo University,Cairo,Egypt
,
Gehan Shahin
Affiliations:
Clinical and Chemical Pathology,Faculty of Medicine, Cairo University,Cairo,Egypt
,
Alaa Eid
Affiliations:
Clinical and Chemical Pathology,Faculty of Medicine, Cairo University,Cairo,Egypt
,
Nehal Diaa
Affiliations:
Clinical and Chemical Pathology,Faculty of Medicine, Cairo University,Cairo,Egypt
Mona El-Ghamrawy
Affiliations:
Pediatrics,Faculty of Medicine, Cairo University,Cairo,Egypt
(Abstract release date: 05/18/17) EHA Library. El-Ghamrawy M. 05/18/17; 182811; PB2097
Mona El-Ghamrawy
Mona El-Ghamrawy
Contributions
Abstract

Abstract: PB2097

Type: Publication Only

Background
Although the etiology of immune thrombocytopenic purpura (ITP) remains unclear, both genetic and environmental factors may contribute to the development of disease. Tumor necrosis factor alpha & beta (TNF-α and TNF-β) are important pro-inflammatory cytokines that play a role in regulation of cell differentiation, proliferation and death, as well as in inflammation, innate and adaptive immune responses, and have been implicated in a wide variety of human diseases. We hypothesized that inflammatory cytokine genes polymorphisms (TNF-α and TNF-β) in ITP pediatric patients may play a fundamental role in pathogenesis of the chronic course of the disease and this might be the base for future specific immunomodulatory therapies for chronic ITP (cITP) in children.

Aims

The current case-control study aimed at detecting TNF-α (-308 G/A) and TNF-β (+252 A/G) genes polymorphism in Egyptian children with cITP and studying their possible association with chronic evolution of the disease.

Methods
The current study included 80 Egyptian cITP patients at Pediatric Hematology Unit, Cairo University (mean age 7.08± 3.64 years) and 100 matched unrelated healthy controls. Genotyping was performed using polymerase chain reaction restriction fragment length polymorphism technique (PCR-RFLP).

Results

TNF-α genotyping revealed that wild G/G, heterozygous G/A and homozygous A/A genotypes among cITP patients were 81.2%, 15% and 3.8% respectively versus 79%, 20% and 1% in control group, while TNF-β wild A/A, heterozygous A/G and homozygous G/G genotypes among cITP patients were 55%, 40% and 5% respectively versus 60%, 28% and 12% in control group, with no statistically significant difference between both groups. Patients having homozygous TNF-α genotype showed statistically significant higher mean age, longer disease duration & lower mean platelet count (p=0.005, 0.024 and 0.008 respectively). TNF-α polymorphism was more frequent among unresponsive patients compared to responsive patients with statistically significant difference. Calculated risk estimation revealed that combined genes polymorphism conferred three fold increased risk of development of cITP (OR=3.491, 95% CI: 1.235-9.869, p=0.015).

Conclusion
We hereby report a strong association between combined polymorphisms of both TNF-α & TNF-β genes and susceptibility to chronicity of ITP in Egyptian children. Further studies for gene polymorphisms which could affect the pathogenesis of ITP and facilitate the development of new therapeutic modalities are recommended.

Session topic: 32. Platelets disorders

Keyword(s): Tumor necrosis factor (TNF), Polymorphism, Cytokine, Chronic ITP

Abstract: PB2097

Type: Publication Only

Background
Although the etiology of immune thrombocytopenic purpura (ITP) remains unclear, both genetic and environmental factors may contribute to the development of disease. Tumor necrosis factor alpha & beta (TNF-α and TNF-β) are important pro-inflammatory cytokines that play a role in regulation of cell differentiation, proliferation and death, as well as in inflammation, innate and adaptive immune responses, and have been implicated in a wide variety of human diseases. We hypothesized that inflammatory cytokine genes polymorphisms (TNF-α and TNF-β) in ITP pediatric patients may play a fundamental role in pathogenesis of the chronic course of the disease and this might be the base for future specific immunomodulatory therapies for chronic ITP (cITP) in children.

Aims

The current case-control study aimed at detecting TNF-α (-308 G/A) and TNF-β (+252 A/G) genes polymorphism in Egyptian children with cITP and studying their possible association with chronic evolution of the disease.

Methods
The current study included 80 Egyptian cITP patients at Pediatric Hematology Unit, Cairo University (mean age 7.08± 3.64 years) and 100 matched unrelated healthy controls. Genotyping was performed using polymerase chain reaction restriction fragment length polymorphism technique (PCR-RFLP).

Results

TNF-α genotyping revealed that wild G/G, heterozygous G/A and homozygous A/A genotypes among cITP patients were 81.2%, 15% and 3.8% respectively versus 79%, 20% and 1% in control group, while TNF-β wild A/A, heterozygous A/G and homozygous G/G genotypes among cITP patients were 55%, 40% and 5% respectively versus 60%, 28% and 12% in control group, with no statistically significant difference between both groups. Patients having homozygous TNF-α genotype showed statistically significant higher mean age, longer disease duration & lower mean platelet count (p=0.005, 0.024 and 0.008 respectively). TNF-α polymorphism was more frequent among unresponsive patients compared to responsive patients with statistically significant difference. Calculated risk estimation revealed that combined genes polymorphism conferred three fold increased risk of development of cITP (OR=3.491, 95% CI: 1.235-9.869, p=0.015).

Conclusion
We hereby report a strong association between combined polymorphisms of both TNF-α & TNF-β genes and susceptibility to chronicity of ITP in Egyptian children. Further studies for gene polymorphisms which could affect the pathogenesis of ITP and facilitate the development of new therapeutic modalities are recommended.

Session topic: 32. Platelets disorders

Keyword(s): Tumor necrosis factor (TNF), Polymorphism, Cytokine, Chronic ITP

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